Association Study Of TCR-CD3 Zeta Gene Polymorphisms And Its MRNA Expression With Rheumatoid Arthritis

ObjectivesRecent evidence has demonstrated that CD3ζ(also called CD247) play a vital role in multiple autoimmune diseases. In this study, we explored the association between CD247 gene single-nucleotide polymorphisms(SNPs) and rheumatoid arthritis(RA) in a Chinese Han population. We also evaluated the CD3ζ expression profile in peripheral blood mononuclear cells(PBMCs) from RA patients and health controls.MethodsThree CD247 polymorphisms(rs704853, rs1214611 and rs858554) were studied in 612 RA patients and 848 controls in a Chinese population. Genotyping was performed using the Fluidigm 192.24 Dynamic Array? Integrated Fluidic Circuit(IFC). For gene expression study, CD3ζ m RNA levels of 36 RA patients and 39 healthy individuals were assessed by RT-PCR. Data were analyzed by SPSS 11.5 software.ResultsA significant association between rs858554 polymorphism and RA was found under all genetic models(all P<0.05). Moreover, we found the genotype distribution and allele frequency of rs858554 were significant associated with ACCP+ and RF+ phenotype as compare to health controls(all P<0.05). Unfortunately, we did not detect any significant associations between rs704853, rs1214611 and RA susceptibility and auto-antibody profiles(all P>0.05).The gene expression assays showed that CD3ζ m RNA levels were down regulated in PBMCs of RA patients when compared to healthy controls(P=0.021). We also found a down-regulation of the CD3ζ chain in ACCP positive RA patients when compared to ACCP negative patients(P=0.038). In addition, CD247 m RNA levels in hyper-active RA were significantly lower than that in inactive RA groups(P=0.005). We observed a negative correlation between CD247 m RNA expression and DAS28 in RA patients(rs =-0.535, P=0.001). However, we didn’t observe any difference of CD3ζ m RNA levels in RF positive RA patients and RF negative patients.We also analyzed whether the possible associated genotypes(A/G and AA+AG of rs858554) were related to CD247 m RNA levels. Unfortunately, we didn’t observe any significant difference in m RNA levels between the two groups(A/G vs. G/G, P=0.114).ConclusionsOur results, the first reported for distinct Chinese populations, support a role of the CD247 gene in the susceptibility to RA. Further studies with more sample size are necessary to clarify the exact role of CD247 gene in the pathogenesis of RA.